The initial objective of this project was to study the interrelationship between lipid, carbohydrate and protein regulation as mediated by glucagon and the simultaneous action of pituitary and adrenal hormones. Our study showed that in the absence of the pituitary and the adrenal, glucagon had risen in blood as measured by the immunoassay, in an amount inconsistent with the level of blood sugar. These data suggest that glucagon secretion at the alpha cell level is regulated not only by blood glucose levels but also by what may be termed a 'permissive' action of both growth hormone and the glucocorticoids. We have extended this work to include a study of the action of glucagon on peripheral tissues in the presence and absence of the liver. There are substantial differences reported in the literature as between the reported peripheral action of glucagon in vivo or in vitro. We use eviscerated rat with and without a functional liver and administer varying amounts of glucagon. We then measure blood levels of glucose, FFA, urea, amino nitrogen, cholesterol and ketone bodies to determine what effect the glucagon has on peripheral tissue metabolism in situ. Our data to date indicate that at least a minimal amount of insulin must be administered prior to the glucagon injection in order to demonstrate an effect of glucagon on peripheral tissues in hepatectomized, eviscerated rats. BIBLIOGRAPHIC REFERENCES: Penhos, J.C. C. Woodbury, Y. Tizabi and E.R. Ramey. Metabolic studies in eviscerated rats with functional livers. Proc. Soc. Expt. Biol. 148:1159-1163, 1975. J. C. Penhos, A. Lepp, and E. R. Ramey. Plasma immunoreactive insulin and immunoreactive glucagon afte evisceration with and without a functional liver. Diabetes 24:637-40, 1975. California.